Abstract:
:Robust determination of the concentration-time profile of anti-infective agents in certain specialized compartments is often limited by the inability to obtain more than a single sample from such a site in any one subject. Vitreous humor and cerebrospinal fluid are obvious examples for which the determination of concentrations of anti-infective agents is limited. Advances in pharmacodynamics have pointed out the importance of understanding the profiles of drugs in the plasma and in specialized compartments in order to dose the drugs to obtain the best patient outcomes. Advances in population pharmacokinetic modeling hold the promise of allowing proper estimation of drug penetration into the vitreous (or other specialized compartment) with only a single vitreous sample, in conjunction with plasma sampling. We have developed a rabbit model which allows multiple samples of vitreous to be obtained without breaking down the blood-vitreous barrier. We have employed this model to test the hypothesis that robust estimates of vitreous penetration by the fluoroquinolone ciprofloxacin can be obtained from a traditional intensive plasma sampling set plus a single vitreous sample. We studied 33 rabbits which were receiving 40 mg of ciprofloxacin per kg of body weight intravenously as short infusions and from which multiple plasma and vitreous samples were obtained and assayed for ciprofloxacin content by high-performance liquid chromatography. Data were analyzed by the iterative two-stage population modeling technique (IT2S), employing the iterative two-stage program of Forrest et al. (Antimicrob. Agents Chemother. 37:1065-1072, 1993). Two data sets were analyzed: all plasma and vitreous samples versus all plasma samples and the initially obtained single vitreous sample. The pharmacokinetic parameter values identified were used to calculate the percent vitreous penetration as the ratio of the area under the concentration-time curve for the vitreous to that for the plasma. The values identified, 4% penetration for the full data set versus 3% penetration for the single vitreous sample data set, and their corresponding estimates were not statistically significantly different. We conclude that population modeling holds promise for the analysis of penetration of antimicrobiol agents into specialized spaces from which only single samples can be obtained, particularly for patients with whom robust plasma sampling can be performed.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Drusano GL,Liu W,Perkins R,Madu A,Madu C,Mayers M,Miller MHdoi
10.1128/aac.39.8.1683subject
Has Abstractpub_date
1995-08-01 00:00:00pages
1683-7issue
8eissn
0066-4804issn
1098-6596journal_volume
39pub_type
杂志文章abstract::Staphylococcus aureus bacteremia (SAB) causes high rates of morbidity and death. Several studies in academic health settings have demonstrated that consultations from infectious diseases specialists improve the quality of care and clinical outcomes for SAB. Few data that describe the impact in resource-limited setting...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00439-16
更新日期:2016-09-23 00:00:00
abstract::Histoplasmosis is a severe infection that affects millions of patients worldwide and is endemic in the Americas. Amphotericin B (AMB) and itraconazole are highly effective for the treatment of severe and milder forms of the disease, but AMB is toxic, and the bioavailability of itraconazole is erratic. Therefore, it is...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01654-13
更新日期:2014-05-01 00:00:00
abstract::The susceptibilities of 87 periodontitis-associated strains of Actinobacillus actinomycetemcomitans to clarithromycin and erythromycin were determined by standard methodology recommended for Haemophilus influenzae. For clarithromycin the MIC at which 90% of the isolates were inhibited was =2.0 microg/ml and the mini...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.11.3000
更新日期:1998-11-01 00:00:00
abstract::Malaria remains a global health burden partly due to Plasmodium parasite resistance to first-line therapeutics. The molecular chaperone heat shock protein 90 (Hsp90) has emerged as an essential protein for blood-stage Plasmodium parasites, but details about its function during malaria's elusive liver stage are unclear...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01799-17
更新日期:2018-03-27 00:00:00
abstract::Penicillin-binding protein (PBP) 2 is the major PBP of five that have been identified in susceptible strains of Staphylococcus aureus. Beta-lactam antibiotic binding to PBP 2 is important for the antibacterial effect. Antibiotic binding to PBP 2 in strain 209P was examined with sodium dodecyl sulfate-polyacrylamide ge...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.3.656
更新日期:1992-03-01 00:00:00
abstract::The results of treatment of 10 patients with anaerobic infections with metronidazole are presented. Six patients were cured, three showed initial good response but circumstances required a change to another drug, and one patient did not respond. The unique spectrum of the drug, its pharmacology, and limitations are di...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/aac.7.5.672
更新日期:1975-05-01 00:00:00
abstract::The efficacy and safety of oral LY217896 for prevention of experimental influenza A/Kawasaki/86 (H1N1) virus infection were assessed in susceptible males randomly assigned to receive LY217896 (75 mg) or placebo once daily for 7 days beginning 24 h prior to viral challenge. The rates of virus shedding (100% in both gro...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1128/aac.38.5.1178
更新日期:1994-05-01 00:00:00
abstract::Targeted antisense and gene replacement mutagenesis experiments demonstrate that only the murA1 gene and not the murA2 gene is required for the normal cellular growth of Bacillus anthracis. Antisense-based modulation of murA1 gene expression hypersensitizes cells to the MurA-specific antibiotic fosfomycin despite the ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01594-07
更新日期:2008-06-01 00:00:00
abstract::Desferrioxamine, a safe and effective iron chelator, was evaluated for its antibacterial and antifungal activity. The susceptibilities of 124 urinary tract isolates and 28 clinical isolates of Neisseria gonorrhoeae to desferrioxamine concentrations that are readily achievable in urine were determined. Of all isolates,...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.25.3.375
更新日期:1984-03-01 00:00:00
abstract::This article reports anti-Toxoplasma gondii activity of 3-(thiophen-2-yl)-1,2,4-triazole-5-thione. The compound displayed significant and reproducible antiparasitic effects at nontoxic concentrations for the host cells, with an experimentally determined 50% inhibitory concentration (IC50) at least 30 times better than...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.03832-14
更新日期:2014-12-01 00:00:00
abstract::The treatment of choice for Stenotrophomonas maltophilia is trimethoprim-sulfamethoxazole (SXT). Fluoroquinolones (FQs) have in vitro activity against S. maltophilia; however, there is limited published information on their effectiveness. The purpose of this study is to compare the effectiveness of FQs and SXT for the...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01324-13
更新日期:2014-01-01 00:00:00
abstract::A total of 621 clinical isolates of Haemophilus influenzae collected in Japan between 1995 and 2003 were studied for their susceptibilities to several antimicrobial agents, beta-lactamase production, and amino acid substitutions in penicillin-binding protein 3 (PBP 3). Over the four study periods (first period, 1995 t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01316-05
更新日期:2006-07-01 00:00:00
abstract::We describe here the in vitro activities of azithromycin, clarithromycin, minocycline, or tigecycline alone and in combination with amphotericin B, itraconazole, terbinafine, voriconazole, anidulafungin, caspofungin, or micafungin against 30 isolates of the oomycete Pythium insidiosum. The assays were based on the CLS...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02349-14
更新日期:2014-09-01 00:00:00
abstract::Although the clinical correlates of the reference antifungal susceptibility test results in hematogenous and deep-seated Candida infection are still controversial, we evaluated the clinical correlates of this test in deep-seated Candida infections in non-AIDS patients. Thirty-two non-AIDS patients with hematogenous or...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/aac.44.10.2715-2718.2000
更新日期:2000-10-01 00:00:00
abstract::Standard therapy of human visceral leishmaniasis with parenteral pentavalent antimonial agents is generally curative but has the disadvantages of a 28-day treatment course, occasional treatment failures, and toxicity. The antifungal and antileishmanial agent amphotericin B has been complexed with lipids to develop a l...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.9.1978
更新日期:1992-09-01 00:00:00
abstract::On the basis of the antiviral action of sulfated polyanions in human immunodeficiency virus and other viral infections, we studied the effect of dextran sulfate and heparin on duck hepatitis B virus infection. These agents do not affect viral uptake and replication in liver cells in vitro or in vivo. Sulfated polyanio...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.11.2431
更新日期:1991-11-01 00:00:00
abstract::In the eubacterial cell, the peptidoglycan is perpetually hydrolyzed throughout the cell cycle by different enzymes such as lytic transglycosylases, endopeptidases, and amidases. In Escherichia coli, four N-acetylmuramoyl-l-alanine amidases, AmiA, -B, -C, and -D, are present in the periplasm. AmiA, -B, and -C are solu...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01520-07
更新日期:2009-07-01 00:00:00
abstract::Pseudomonas aeruginosa is a multidrug-resistant nosocomial pathogen. We showed previously that thiostrepton (TS), a Gram-positive thiopeptide antibiotic, is imported via pyoverdine receptors and synergizes with iron chelator deferasirox (DSX) to inhibit the growth of P. aeruginosa and Acinetobacter baumannii clinical ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01909-19
更新日期:2020-02-21 00:00:00
abstract::We assessed prophylactic or continuous therapy of isavuconazole, posaconazole, or voriconazole in treating pulmonary murine mucormycosis. In the prophylaxis studies, only isavuconazole treatment resulted in significantly improved survival and lowered tissue fungal burden of immunosuppressed mice infected with Rhizopus...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02589-16
更新日期:2017-04-24 00:00:00
abstract::Thirty-five strains of Pasteurella multocida from humans and animals were tested for susceptibility to five cephalosporins by a broth dilution method. Cefcanel showed high activity against all isolates (MIC and MBC, less than or equal to 0.64 micrograms/ml). The corresponding figure for cefaclor and cefuroxime was 2.5...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.12.2142
更新日期:1989-12-01 00:00:00
abstract::Here we completely sequenced four mcr-1-haboring plasmids, isolated from two extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli and two carbapenemase-producing Klebsiella pneumoniae clinical isolates. The mcr-1-harboring plasmids from an E. coli sequence type 2448 (ST2448) isolate and two K. pneumoniae ST...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00550-16
更新日期:2016-06-20 00:00:00
abstract::Passive antibody administration is a potentially useful approach for the therapy of human Cryptococcus neoformans infections. To evaluate the efficacy of the human immunoglobulin G1 (IgG1) constant region against C. neoformans and to construct murine antibody derivatives with reduced immunogenicities and longer half-l...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.7.1507
更新日期:1994-07-01 00:00:00
abstract::In concert with the development of novel beta-lactams and broad-spectrum cephalosporins, bacterially encoded beta-lactamases have evolved to accommodate the new agents. This study was designed to identify, at the sequence level, the genes responsible for the extended-spectrum-beta-lactamase (ESBL) phenotypes of Escher...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00883-08
更新日期:2009-02-01 00:00:00
abstract::Most manifestations of candidiasis are associated with biofilm formation on biological or inanimate surfaces. Candida albicans biofilms are recalcitrant to treatment with conventional antifungal therapies. Here we report on the activity of caspofungin, a new semisynthetic echinocandin, against C. albicans biofilms. Ca...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.11.3591-3596.2002
更新日期:2002-11-01 00:00:00
abstract::The aromatic diamidines represent a class of compounds with broad-spectrum antimicrobial activity; however, their development is hindered by a lack of understanding of their mechanism of antimicrobial action. DB75 [2,5-bis(4-amidinophenyl)furan] is a trypanocidal aromatic diamidine that was originally developed as a s...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.10.3968-3974.2004
更新日期:2004-10-01 00:00:00
abstract::A series of quaternary ammonium compounds that are esters of betaine and fatty alcohols with hydrocarbon chain lengths of 10 to 18 carbon atoms were tested with respect to antimicrobial activities and rates of hydrolysis. When the tetradecyl derivative was tested against some selected microorganisms, the killing effec...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.10.1949
更新日期:1990-10-01 00:00:00
abstract::In vitro surveys of antimicrobial resistance among clinically important anaerobes are an important source of information that can be used for clinical decisions in the choice of empiric antimicrobial therapy. This study surveyed the susceptibilities of 556 clinical anaerobic isolates from four large medical centers us...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
doi:10.1128/AAC.45.4.1238-1243.2001
更新日期:2001-04-01 00:00:00
abstract::Bacteriophage therapy is a promising alternative treatment to antibiotics, as it has been documented to be efficacious against multidrug-resistant bacteria with minimal side effects. Several groups have demonstrated the efficacy of phage suspension in vivo to treat lung infections using intranasal delivery; however, p...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01714-17
更新日期:2018-01-25 00:00:00
abstract::The biological availability of cefoxitin administered rectally in the form of suppositories was examined in six human subjects by a cross-over design. Four different suppository systems containing adjuvants expected to enhance the absorption of the drug were studied. The presence of sodium salicylate and a nonionic su...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1128/aac.28.2.211
更新日期:1985-08-01 00:00:00
abstract::As the site of insertion of the aadB gene cassette on pRAY, from a clinical isolate of Acinetobacter, is almost identical to the preferred site on integrons, the composite 59-base element (59-BE) associated with this cassette is potentially recombinationally active. By using a conduction assay to quantitate site activ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.10.2538
更新日期:1999-10-01 00:00:00